Combination of ciprofloxacin/celecoxib as a novel therapeutic strategy for ALS.

OBJECTIVE: This study aimed to evaluate the safety and tolerability of a fixed-dose co-formulation of ciprofloxacin and celecoxib (PrimeC) in patients with amyotrophic lateral sclerosis (ALS), and to examine its effects on disease progression and ALS-related biomarkers. METHODS: In this proof of concept, open-label, phase IIa study of PrimeC in 15 patients with ALS, participants were administered PrimeC thrice daily for 12 months. The primary endpoints were safety and tolerability. Exploratory endpoints included disease progression outcomes such as forced vital capacity, revised ALS functional rating scale, and effect on algorithm-predicted survival. In addition, indications of a biological effect were assessed by selected biomarker analyses, including TDP-43 and LC3 levels in neuron-derived exosomes (NDEs), and serum neurofilaments. RESULTS: Four participants experienced adverse events (AEs) related to the study drug. None of these AEs were unexpected, and most were mild or moderate (69%). Additionally, no serious AEs were related to the study drug. One participant tested positive for COVID-19 and recovered without complications, and no other abnormal laboratory investigations were found. Participants' survival compared to their predictions showed no safety concerns. Biomarker analyses demonstrated significant changes associated with PrimeC in neural-derived exosomal TDP-43 levels and levels of LC3, a key autophagy marker. INTERPRETATION: This study supports the safety and tolerability of PrimeC in ALS. Biomarker analyses suggest early evidence of a biological effect. A placebo-controlled trial is required to disentangle the biomarker results from natural progression and to evaluate the efficacy of PrimeC for the treatment of ALS. Summary for social media if publishedTwitter handles: @NeurosenseT, @ShiranZimri•What is the current knowledge on the topic? ALS is a severe neurodegenerative disease, causing death within 2-5 years from diagnosis. To date there is no effective treatment to halt or significantly delay disease progression.•What question did this study address? This study assessed the safety, tolerability and exploratory efficacy of PrimeC, a fixed dose co-formulation of ciprofloxacin and celecoxib in the ALS population.•What does this study add to our knowledge? This study supports the safety and tolerability of PrimeC in ALS, and exploratory biomarker analyses suggest early insight for disease related-alteration.•How might this potentially impact the practice of neurology? These results set the stage for a larger, placebo-controlled study to examine the efficacy of PrimeC, with the potential to become a new drug candidate for ALS.

Evaluation of cell salvage autotransfusion utility during liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) may be associated with massive blood loss and the need for allogenic blood product transfusions. Cell salvage autotransfusion (CS) is an attractive alternative to allogenic red blood cell (RBC) transfusion. However, controversy surrounds its usefulness during OLT; some studies stated that CS decreased transfusions of allogenic blood products and others stated that blood loss was increased. The aim of this study was to evaluate the efficiency of the CS during OLT. PATIENTS AND METHODS: After approval by the institutional ethics committee, a prospective survey was undertaken. A total of 150 consecutive OLTs were included in the study. Two groups of patients were formed. Period 1 included patients 1-75 with no CS use. Period 2 comprised patients 76-150 with systematic CS use. RESULTS: Patients from both periods were comparable. CS was used in all cases in period 2, and there was enough salvaged blood to retransfuse 65% of these OLTs. The mean volume of retransfused blood was 338+/-339 ml. The transfusion rate did not change from period 1 to period 2. The mean number of RBC units transfused per patient was 0.4+/-0.9 vs 0.4+/-1.2 with 78.7% vs 81.3% of cases not receiving transfusion of any blood product. The threshold for RBC transfusions was the same. The length of surgery and blood loss were greater in period 2 than in period 1 (associated with the arrival of two junior surgeons), but the hemoglobin (Hb) value was also higher at the end of surgery (93.8+/-19.3 g/L vs 85.2+/-17.8 g/L, p<0.0001). CONCLUSION: Despite increased blood loss in period 2, CS saved 21 g/L of Hb per patient or two RBC unit transfusions. As long as we cannot predict with accuracy which patients will bleed, we will continue to use the CS for all OLTs.